A semi-empirical glycosylation model of a camelid monoclonal antibody under hypothermia cell culture conditions. (1st July 2017)

• Record Type: Journal Article
• Authors: Aghamohseni, Hengameh; Spearman, Maureen; Ohadi, Kaveh; Braasch, Katrin; Moo-Young, Murray; Butler, Michael; Budman, Hector M
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 44:Number 7(2017)
• Page Start: 1005
• Page End: 1020
• Publication Date: 2017-07-01
• Subjects: Chinese hamster ovary cells -- Monoclonal antibody -- Hypothermia -- Glycosylation -- Mathematical modeling; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1007/s10295-017-1926-z
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubation temperatures of (33 and 37 °C) in batch operation mode. Hypothermia was applied either through the entire culture duration or only during the post-exponential phase. Beyond reducing cell growth and increasing productivity, hypothermia significantly altered the galactosylation index profiles as compared to control conditions. A novel semi-empirical dynamic model was proposed for elucidating the connections between the extracellular cell culture conditions to galactosylation index. The developed model is based on a simplified balance of nucleotides sugars and on the correlation between sugars' levels to the galactosylation index (GI). The model predictions were found to be in a good agreement with the experimental data. The proposed empirical model is expected to be useful for controlling the glycoprofiles by manipulating culture conditions.